Antibacterial activities and conformations of bovine β-defensin BNBD-12 and analogs: structural and disulfide bridge requirements for activity

Abstract

Structure and biological activities of synthetic peptides corresponding to bovine neutrophil β-defensin BNBD-12, GPLSC¹GRNGGVC²IPIR^C3 PVPMRQIGTC⁴ FGRPVKC⁵ C⁶RSW with disulfide connectivities C¹-C⁵, C²-C⁴ and C³-C⁶ and its variants with one, two and three disulfide bridges have been investigated. Selective protection of cysteine thiols was necessary in the four and six cysteine containing peptides for the formation of disulfide connectivities as observed in BNBD-12. Circular dichroism (CD) spectra indicate that in aqueous medium, only a small fraction of molecules populate turn-like conformations. In the presence of micelles and lipid vesicles, the single, two and three disulfide containing peptides adopt β-hairpin or β-sheet structures. Antibacterial activity was observed for all the peptides, irrespective of the number of disulfide bridges or how they were connected. Our results suggest that a rigid β-sheet structure or the presence of three disulfide bridges does not appear to be stringent requirements for antibacterial activity in β-defensins.